Ovarian Neoplasms
Conditions
Brief summary
This is an international, randomized phase II trial. The aim is to assess the efficacy and the safety of BI 6727 Versus investigator's best choice single agent cytotoxic in recurrent third and fourth lines platinum resistant/refractory ovarian cancer. 100 patients will be randomised at the study entry to receive either BI 6727 (Arm A: 50 patients) or non-platinum single agent cytotoxic (Arm B: 50 patients) Treatment will be continued until disease progression or unacceptable toxicity. Primary endpoint: disease control rate at week 24 according to Response Evaluation Criteria In Solid Tumours version 1.1. Secondary endpoints: efficacy (progression free survival, overall survival, biological tumour response, biological progression free survival assessed by serum CA 125 according to Gynecologic Cancer Intergroup criteria, safety according to the NCI CTCAE v.3, disease symptoms control assessed by the EORTC QLQ-C30, QLQ-OV28 and individual symptoms questionnaires, pharmacokinetics of BI 6727. Others endpoints: biomarkers and pharmacogenetics analysis (optional)
Interventions
DRUGPaclitaxel
Patients receive paclitaxel in a 4 week schedule
DRUGGemcitabine
Patients receive gemcitabine in a 3 week schedule
DRUGTopotecan
Patients receive topotecan in 3 or 4 week schedule
DRUGPegylated liposomal doxorubicin (PLD)
Patients receive PLD in a 4 week schedule
DRUGBI 6727
Patients receive BI 6727 infusion every 3 weeks
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Confirmed recurrent epithelial ovarian carcinoma, peritoneal carcinoma or fallopian tube carcinoma. 2. Platinum resistant or platinum refractory disease. 3. Eastern Collaborative Oncology Group performance status \< = 2. 4. Life expectancy \> = 3 months. 5. At least one measurable lesion (Response Evaluation Criteria In Solid Tumours version 1.1). 6. Adequate hepatic, renal and bone marrow functions. 7. signed written informed consent prior to admission to the study.
Exclusion criteria
1. Contre-indications for cytotoxic treatment according to the Summary of Product Characteristics (Arm B). 2. Clinical evidence of active brain metastasis or leptomeningeal involvement. 3. Other malignancy currently requiring active therapy. 4. QTc prolongation according to Fridericia formula deemed clinically relevant by the investigator (e.g., congenital long QT syndrome, QTc according to Fridericia formula \> 470 ms). 5. Hypersensitivity to one of the trial drugs or the excipients. 6. Serious illness or concomitant non- oncological disease. 7. Systemic anticancer therapy within 4 weeks before the start of the study. 8. Evidence of ileus sor sub ileus.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) at Week 24 According to Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1 | Week 24 | DCR was defined as the proportion of patients who had an overall response of complete response (CR), partial response (PR), or stable disease (SD). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization until death or study discontinuation; Up to 213 weeks | OS is defined as time from randomisation to death irrespective of the cause of the death. |
| Best Overall Response | time from the date of randomisation until study completion/discontinuation; Up to 213 weeks | Best overall response (BOR) is defined as the best response recorded at any time from the date of randomisation until the end of treatment. Missing categories signify that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed. |
| Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria | At screening and every 6 weeks thereafter (Up to 213 weeks) | Patients were to have a pre-treatment CA-125 of at least twice the upper limit of normal to be considered for CA-125 response. Patients were not evaluable by CA-125 if they had received mouse antibodies or if they had undergone medical and/or surgical interference with their peritoneum or pleura during the previous 28 days. In eligible patients, a CA-125 response was defined as the moment the CA- 25 was reduced by 50%, with this being confirmed with a consecutive CA-125 assessment not earlier than 28 days after the previous one. Biological response rate based on serum CA-125 levels was assessed according to the guidelines by the Gynaecologic Cancer Intergroup. Monitoring of blood levels of the tumour marker CA-125 was performed at screening and every 6 weeks thereafter. |
| Biological Progression-free Survival Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria | At screening and every 6 weeks thereafter (Up to 213 weeks ) | Biological PFS including assessment of CA-125 levels was defined as the time from randomisation until the first occurrence of progressive disease according to CA-125, progressive disease according to radiological evidence, or death. Also according to the below criterias, * In patients with radiological measurable disease, disease progression during study treatment could not be declared on the basis of CA-125 alone. * Patients with elevated CA-125 pre-treatment and normalization of CA-125 had to show evidence of CA-125 ≥ to two times the upper normal limit on two occasions at least one week apart or * Patients with elevated CA-125 pre-treatment, which never normalized, had to show evidence of CA-125 ≥ to two times the nadir value on two occasions at least one week apart or * Patients with CA-125 in the normal range pre-treatment had to show evidence of CA-125 ≥ to two times the upper normal limit on two occasions at least one week apart. |
| Time to Deterioration in Global Health Status/Quality of Life (QOL) | Every 6 weeks (Up to 213 weeks ) | Time to deterioration in global health status/Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires. The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death. |
| Time to Deterioration in Fatigue/Quality of Life (QOL) | Every 6 weeks (Up to 213 weeks ) | Time to deterioration in fatigue/Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires. The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death. |
| Time to Deterioration in Pain/ Quality of Life (QOL) | Every 6 weeks (Up to 213 weeks ) | Time to deterioration in pain/ Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires. The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death. |
| Time to Deterioration in Abdominal Bloating/ Quality of Life (QOL) | Every 6 weeks (Up to 213 weeks ) | Time to deterioration in abdominal bloating/ Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires. The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death. |
| Time to Deterioration in the Three Most Troublesome Disease Specific Symptoms/ Quality of Life (QOL) | Every 6 weeks (Up to 213 weeks) | Three most troublesome disease specific symptoms, defined by the patient at baseline. Patients that have defined more than 3 most troublesome symptoms have not been taken into account in the analysis. Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires. The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death. |
| Cmax; Maximum Measured Concentration of CD 10899 BS in Plasma | -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration | Cmax; maximum measured concentration of CD 10899 BS (metabolite of Volasertib BI 6727) in plasma |
| Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | From first treatment administration to 21 days after the last drug administration (Up to 1403 days) | Incidence and intensity of adverse events according to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 |
| Clinically Relevant Changes in Laboratory and ECG Data | From first treatment administration to 21 days after the last drug administration (Up to 1403 days) | Clinically relevant changes in laboratory and ECG data |
| Progression Free Survival (PFS) | From randomization until disease progression, death or study discontinuation; Up to 213 weeks | Progression-free survival of a patient was based on the investigator's assessment; it was defined as the number of days from the date of randomisation until the date of either disease progression or death from any cause, whichever occurred first. Definition of disease progression according to RECIST version 1.1; Patients with measurable tumour lesions at baseline, Target-lesions: at least a 20% increase in the sum of diameters of target lesions, the sum of diameters must also demonstrate an absolute increase of at least 5 mm,taking as reference the smallest sum on study, or appearance of 1 or more new lesions. Non-target lesions: unequivocal progression of existing non-target lesions or appearance of 1 or more new lesions Patients with non-measurable tumour lesions at baseline, Non-target lesions: requires unequivocal progression of existing non-target lesions or appearance of 1 or more new lesions |
| AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for CD 10899 BS | -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration | AUC (0-24); area under the concentration-time curve in plasma over the time interval from 0 to 24 hours for CD 10899 BS (metabolite of Volasertib BI 6727) |
| AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for BI 6727 BS | -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration | AUC (0-inf); area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity for BI 6727 BS |
| AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for CD 10899 BS | -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration | AUC (0-inf); area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity for CD 10899 BS (metabolite of Volasertib BI 6727) |
| Cmax; Maximum Measured Concentration of BI 6727 BS in Plasma | -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration | Cmax; maximum measured concentration of BI 6727 BS in plasma |
| Tmax; Time From Dosing to Maximum Measured Concentration of BI 6727 BS in Plasma | -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration | tmax; time from dosing to maximum measured concentration of BI 6727 BS in plasma |
| Tmax; Time From Dosing to Maximum Measured Concentration of CD 10899 BS in Plasma | -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration | tmax; time from dosing to maximum measured concentration of CD 10899 BS (metabolite of Volasertib BI 6727) in plasma |
| t1/2; Terminal Half-life of BI 6727 BS in Plasma | -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration | t1/2; Terminal half-life of BI 6727 BS in plasma |
| t1/2; Terminal Half-life of CD 10899 BS in Plasma | -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration | t1/2; Terminal half-life of CD 10899 BS in plasma |
| MRT; Mean Residence Time of BI 6727 BS in the Body | -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration | MRT; Mean residence time of BI 6727 BS in the body |
| CL; Total Clearance of BI 6727 BS in Plasma After Intravenous Administration | -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration | CL; total clearance of BI 6727 BS in plasma after intravenous administration |
| Vss;Apparent Volume of Distribution at Steady State Following Intravenous Administration for BI 6727 BS | -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration | Vss;apparent volume of distribution at steady state following intravenous administration for BI 6727 BS |
| Biomarkers and Pharmacogenetics Analysis (Optional) | 6 months | This endpoint has not been statistically analysed in the study report |
| AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for BI 6727 BS | -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration | AUC (0-24); area under the concentration-time curve in plasma over the time interval from 0 to 24 hours for BI 6727 BS |
Countries
Belgium, France, Slovakia, Spain, Sweden
Participant flow
Recruitment details
Overall 54 patients were treated in Volasertib arm and 55 patients were treated in Cytotoxic arm. The Not completed category in the Subject Disposition table represents Treatment permanently discontinued and The reasons for non-completion in the table represent Reason for treatment discontinuation.
Participants by arm
| Arm | Count |
|---|---|
| Volasertib (BI 6727) Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course.
Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status. | 54 |
| Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer:
* Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days)
* Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days)
* Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days)
* Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days) | 55 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Non-compliant with protocol | 0 | 2 |
| Overall Study | Not treated | 1 | 0 |
| Overall Study | Other AE | 3 | 10 |
| Overall Study | Progressive disease RECIST | 44 | 28 |
| Overall Study | Reason other than specified above | 2 | 6 |
| Overall Study | Refused continuation of study med. | 1 | 2 |
| Overall Study | Wors. or AE of underlying cancer disease | 4 | 6 |
Baseline characteristics
| Characteristic | Volasertib (BI 6727) | Cytotoxic | Total |
|---|---|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 9.88 | 60.9 years STANDARD_DEVIATION 9.26 | 61.1 years STANDARD_DEVIATION 9.53 |
| Sex: Female, Male Female | 54 Participants | 55 Participants | 109 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 53 / 54 | 53 / 55 | 21 / 24 |
| serious Total, serious adverse events | 24 / 54 | 19 / 55 | 12 / 24 |
Outcome results
Primary
Disease Control Rate (DCR) at Week 24 According to Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1
DCR was defined as the proportion of patients who had an overall response of complete response (CR), partial response (PR), or stable disease (SD).
Time frame: Week 24
Population: TS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Volasertib (BI 6727) | Disease Control Rate (DCR) at Week 24 According to Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1 | 30.6 percentage of participants |
| Cytotoxic | Disease Control Rate (DCR) at Week 24 According to Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1 | 43.1 percentage of participants |
Comparison: Kaplan Meier estimates and confidence intervals (CI) were calculated using Greenwood's variance estimate within each treatment arm and the asymptotic CI for the difference in the rates found. The time was censored in those cases where there was no death or progression until the last trial visit95% CI: [-31.1, 6]
Secondary
AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for BI 6727 BS
AUC (0-24); area under the concentration-time curve in plasma over the time interval from 0 to 24 hours for BI 6727 BS
Time frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Volasertib (BI 6727) | AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for BI 6727 BS | 2140 ng*h/mL | Geometric Coefficient of Variation 25.5 |
Secondary
AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for CD 10899 BS
AUC (0-24); area under the concentration-time curve in plasma over the time interval from 0 to 24 hours for CD 10899 BS (metabolite of Volasertib BI 6727)
Time frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Volasertib (BI 6727) | AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for CD 10899 BS | 204 ng*h/mL | Geometric Coefficient of Variation 65.3 |
Secondary
AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for BI 6727 BS
AUC (0-inf); area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity for BI 6727 BS
Time frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Volasertib (BI 6727) | AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for BI 6727 BS | 6240 ng*h/mL | Geometric Coefficient of Variation 29.8 |
Secondary
AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for CD 10899 BS
AUC (0-inf); area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity for CD 10899 BS (metabolite of Volasertib BI 6727)
Time frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Volasertib (BI 6727) | AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for CD 10899 BS | 1400 ng*h/mL | Geometric Coefficient of Variation 35.8 |
Secondary
Best Overall Response
Best overall response (BOR) is defined as the best response recorded at any time from the date of randomisation until the end of treatment. Missing categories signify that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed.
Time frame: time from the date of randomisation until study completion/discontinuation; Up to 213 weeks
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Volasertib (BI 6727) | Best Overall Response | PR- Measurable disease | 7 participants |
| Volasertib (BI 6727) | Best Overall Response | CR- Non-measurable disease | 0 participants |
| Volasertib (BI 6727) | Best Overall Response | PD- Measurable disease | 14 participants |
| Volasertib (BI 6727) | Best Overall Response | Non-CR/Non-PD- Non-measurable disease | 6 participants |
| Volasertib (BI 6727) | Best Overall Response | SD- Measurable disease | 24 participants |
| Volasertib (BI 6727) | Best Overall Response | PD- Non-measurable disease | 3 participants |
| Volasertib (BI 6727) | Best Overall Response | Missing- Measurable disease | 0 participants |
| Volasertib (BI 6727) | Best Overall Response | Missing- Non-measurable disease | 0 participants |
| Volasertib (BI 6727) | Best Overall Response | CR- Measurable disease | 0 participants |
| Cytotoxic | Best Overall Response | Missing- Non-measurable disease | 1 participants |
| Cytotoxic | Best Overall Response | CR- Measurable disease | 0 participants |
| Cytotoxic | Best Overall Response | PR- Measurable disease | 8 participants |
| Cytotoxic | Best Overall Response | SD- Measurable disease | 24 participants |
| Cytotoxic | Best Overall Response | PD- Measurable disease | 10 participants |
| Cytotoxic | Best Overall Response | Missing- Measurable disease | 2 participants |
| Cytotoxic | Best Overall Response | CR- Non-measurable disease | 1 participants |
| Cytotoxic | Best Overall Response | Non-CR/Non-PD- Non-measurable disease | 9 participants |
| Cytotoxic | Best Overall Response | PD- Non-measurable disease | 0 participants |
Secondary
Biological Progression-free Survival Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria
Biological PFS including assessment of CA-125 levels was defined as the time from randomisation until the first occurrence of progressive disease according to CA-125, progressive disease according to radiological evidence, or death. Also according to the below criterias, * In patients with radiological measurable disease, disease progression during study treatment could not be declared on the basis of CA-125 alone. * Patients with elevated CA-125 pre-treatment and normalization of CA-125 had to show evidence of CA-125 ≥ to two times the upper normal limit on two occasions at least one week apart or * Patients with elevated CA-125 pre-treatment, which never normalized, had to show evidence of CA-125 ≥ to two times the nadir value on two occasions at least one week apart or * Patients with CA-125 in the normal range pre-treatment had to show evidence of CA-125 ≥ to two times the upper normal limit on two occasions at least one week apart.
Time frame: At screening and every 6 weeks thereafter (Up to 213 weeks )
Population: TS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Volasertib (BI 6727) | Biological Progression-free Survival Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria | 13.1 weeks |
| Cytotoxic | Biological Progression-free Survival Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria | 20.6 weeks |
95% CI: [0.73, 1.7]
Secondary
Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria
Patients were to have a pre-treatment CA-125 of at least twice the upper limit of normal to be considered for CA-125 response. Patients were not evaluable by CA-125 if they had received mouse antibodies or if they had undergone medical and/or surgical interference with their peritoneum or pleura during the previous 28 days. In eligible patients, a CA-125 response was defined as the moment the CA- 25 was reduced by 50%, with this being confirmed with a consecutive CA-125 assessment not earlier than 28 days after the previous one. Biological response rate based on serum CA-125 levels was assessed according to the guidelines by the Gynaecologic Cancer Intergroup. Monitoring of blood levels of the tumour marker CA-125 was performed at screening and every 6 weeks thereafter.
Time frame: At screening and every 6 weeks thereafter (Up to 213 weeks)
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Volasertib (BI 6727) | Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria | Yes | 10 participants |
| Volasertib (BI 6727) | Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria | No | 33 participants |
| Volasertib (BI 6727) | Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria | Not evaluable | 4 participants |
| Volasertib (BI 6727) | Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria | Missing | 7 participants |
| Cytotoxic | Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria | Missing | 9 participants |
| Cytotoxic | Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria | Yes | 12 participants |
| Cytotoxic | Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria | Not evaluable | 11 participants |
| Cytotoxic | Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria | No | 23 participants |
Secondary
Biomarkers and Pharmacogenetics Analysis (Optional)
This endpoint has not been statistically analysed in the study report
Time frame: 6 months
Secondary
Clinically Relevant Changes in Laboratory and ECG Data
Clinically relevant changes in laboratory and ECG data
Time frame: From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Alanine aminotransferase decreased | 1.9 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Electrocardiogram QT prolonged | 0.0 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Alanine aminotransferase increased | 1.9 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Blood urea increased | 1.9 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Haemoglobin decreased | 3.7 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Transaminases increased | 0.0 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | White blood cell count decreased | 3.7 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Neutrophil count decreased | 1.9 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Blood potassium decreased | 1.9 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Blood magnesium decreased | 3.7 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Troponin I increased | 0.0 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Aspartate aminotransferase increased | 3.7 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Blood lactate dehydrogenase increased | 3.7 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Aspartate aminotransferase abnormal | 0.0 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Blood creatine phosphokinase decreased | 1.9 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Blood uric acid increased | 1.9 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Platelet count decreased | 9.3 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Blood alkaline phosphatase increased | 3.7 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Gamma-glutamyltransferase increased | 3.7 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Blood creatinine increased | 9.3 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Blood bilirubin increased | 1.9 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Alanine aminotransferase abnormal | 0.0 percentage of participants |
| Volasertib (BI 6727) | Clinically Relevant Changes in Laboratory and ECG Data | Hepatic enzyme increased | 1.9 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Blood bilirubin increased | 0.0 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Blood alkaline phosphatase increased | 12.7 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Blood creatinine increased | 3.6 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Platelet count decreased | 0.0 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Alanine aminotransferase increased | 9.1 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Aspartate aminotransferase increased | 5.5 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Blood uric acid increased | 5.5 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Gamma-glutamyltransferase increased | 5.5 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Alanine aminotransferase abnormal | 0.0 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Electrocardiogram QT prolonged | 0.0 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Haemoglobin decreased | 3.6 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Neutrophil count decreased | 0.0 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Troponin I increased | 0.0 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Blood lactate dehydrogenase increased | 0.0 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Blood magnesium decreased | 0.0 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | White blood cell count decreased | 0.0 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Blood urea increased | 3.6 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Alanine aminotransferase decreased | 0.0 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Blood creatine phosphokinase decreased | 0.0 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Blood potassium decreased | 0.0 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Hepatic enzyme increased | 0.0 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Aspartate aminotransferase abnormal | 1.8 percentage of participants |
| Cytotoxic | Clinically Relevant Changes in Laboratory and ECG Data | Transaminases increased | 1.8 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Hepatic enzyme increased | 0.0 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Blood urea increased | 0.0 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Alanine aminotransferase abnormal | 4.2 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Blood creatinine increased | 0.0 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Alanine aminotransferase decreased | 0.0 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Gamma-glutamyltransferase increased | 4.2 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Blood uric acid increased | 0.0 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Blood bilirubin increased | 0.0 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Aspartate aminotransferase increased | 4.2 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Transaminases increased | 0.0 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Blood creatine phosphokinase decreased | 0.0 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Alanine aminotransferase increased | 4.2 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Aspartate aminotransferase abnormal | 0.0 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Troponin I increased | 4.2 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Blood potassium decreased | 0.0 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Blood lactate dehydrogenase increased | 0.0 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Neutrophil count decreased | 4.2 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Platelet count decreased | 8.3 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Blood magnesium decreased | 0.0 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Haemoglobin decreased | 4.2 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Blood alkaline phosphatase increased | 8.3 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | White blood cell count decreased | 0.0 percentage of participants |
| Cytotoxic to Volasertib Switch | Clinically Relevant Changes in Laboratory and ECG Data | Electrocardiogram QT prolonged | 4.2 percentage of participants |
Secondary
CL; Total Clearance of BI 6727 BS in Plasma After Intravenous Administration
CL; total clearance of BI 6727 BS in plasma after intravenous administration
Time frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Volasertib (BI 6727) | CL; Total Clearance of BI 6727 BS in Plasma After Intravenous Administration | 801 mL/min | Geometric Coefficient of Variation 29.8 |
Secondary
Cmax; Maximum Measured Concentration of BI 6727 BS in Plasma
Cmax; maximum measured concentration of BI 6727 BS in plasma
Time frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Volasertib (BI 6727) | Cmax; Maximum Measured Concentration of BI 6727 BS in Plasma | 341 ng/mL | Geometric Coefficient of Variation 42.2 |
Secondary
Cmax; Maximum Measured Concentration of CD 10899 BS in Plasma
Cmax; maximum measured concentration of CD 10899 BS (metabolite of Volasertib BI 6727) in plasma
Time frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Volasertib (BI 6727) | Cmax; Maximum Measured Concentration of CD 10899 BS in Plasma | 10.8 ng/mL | Geometric Coefficient of Variation 63.4 |
Secondary
Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Incidence and intensity of adverse events according to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time frame: From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Volasertib (BI 6727) | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 4 | 25 participants |
| Volasertib (BI 6727) | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 3 | 16 participants |
| Volasertib (BI 6727) | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 1 | 4 participants |
| Volasertib (BI 6727) | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 2 | 6 participants |
| Volasertib (BI 6727) | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 5 | 3 participants |
| Cytotoxic | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 3 | 25 participants |
| Cytotoxic | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 1 | 3 participants |
| Cytotoxic | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 2 | 19 participants |
| Cytotoxic | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 4 | 5 participants |
| Cytotoxic | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 5 | 3 participants |
| Cytotoxic to Volasertib Switch | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 5 | 3 participants |
| Cytotoxic to Volasertib Switch | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 4 | 6 participants |
| Cytotoxic to Volasertib Switch | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 1 | 1 participants |
| Cytotoxic to Volasertib Switch | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 3 | 9 participants |
| Cytotoxic to Volasertib Switch | Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Grade 2 | 3 participants |
Secondary
MRT; Mean Residence Time of BI 6727 BS in the Body
MRT; Mean residence time of BI 6727 BS in the body
Time frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Volasertib (BI 6727) | MRT; Mean Residence Time of BI 6727 BS in the Body | 118 hours | Geometric Coefficient of Variation 31.2 |
Secondary
Overall Survival (OS)
OS is defined as time from randomisation to death irrespective of the cause of the death.
Time frame: From randomization until death or study discontinuation; Up to 213 weeks
Population: TS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Volasertib (BI 6727) | Overall Survival (OS) | 60.1 weeks |
| Cytotoxic | Overall Survival (OS) | 68.6 weeks |
95% CI: [0.63, 1.42]
Secondary
Progression Free Survival (PFS)
Progression-free survival of a patient was based on the investigator's assessment; it was defined as the number of days from the date of randomisation until the date of either disease progression or death from any cause, whichever occurred first. Definition of disease progression according to RECIST version 1.1; Patients with measurable tumour lesions at baseline, Target-lesions: at least a 20% increase in the sum of diameters of target lesions, the sum of diameters must also demonstrate an absolute increase of at least 5 mm,taking as reference the smallest sum on study, or appearance of 1 or more new lesions. Non-target lesions: unequivocal progression of existing non-target lesions or appearance of 1 or more new lesions Patients with non-measurable tumour lesions at baseline, Non-target lesions: requires unequivocal progression of existing non-target lesions or appearance of 1 or more new lesions
Time frame: From randomization until disease progression, death or study discontinuation; Up to 213 weeks
Population: TS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Volasertib (BI 6727) | Progression Free Survival (PFS) | 13.1 weeks |
| Cytotoxic | Progression Free Survival (PFS) | 20.6 weeks |
95% CI: [0.66, 1.53]
Secondary
t1/2; Terminal Half-life of BI 6727 BS in Plasma
t1/2; Terminal half-life of BI 6727 BS in plasma
Time frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Volasertib (BI 6727) | t1/2; Terminal Half-life of BI 6727 BS in Plasma | 143 hours | Geometric Coefficient of Variation 21.3 |
Secondary
t1/2; Terminal Half-life of CD 10899 BS in Plasma
t1/2; Terminal half-life of CD 10899 BS in plasma
Time frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Volasertib (BI 6727) | t1/2; Terminal Half-life of CD 10899 BS in Plasma | 146 hours | Geometric Coefficient of Variation 21.5 |
Secondary
Time to Deterioration in Abdominal Bloating/ Quality of Life (QOL)
Time to deterioration in abdominal bloating/ Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires. The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.
Time frame: Every 6 weeks (Up to 213 weeks )
Population: TS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Volasertib (BI 6727) | Time to Deterioration in Abdominal Bloating/ Quality of Life (QOL) | NA weeks |
| Cytotoxic | Time to Deterioration in Abdominal Bloating/ Quality of Life (QOL) | 47.2 weeks |
95% CI: [0.33, 1.47]
Secondary
Time to Deterioration in Fatigue/Quality of Life (QOL)
Time to deterioration in fatigue/Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires. The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.
Time frame: Every 6 weeks (Up to 213 weeks )
Population: TS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Volasertib (BI 6727) | Time to Deterioration in Fatigue/Quality of Life (QOL) | NA weeks |
| Cytotoxic | Time to Deterioration in Fatigue/Quality of Life (QOL) | 67.1 weeks |
95% CI: [0.37, 1.65]
Secondary
Time to Deterioration in Global Health Status/Quality of Life (QOL)
Time to deterioration in global health status/Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires. The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.
Time frame: Every 6 weeks (Up to 213 weeks )
Population: TS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Volasertib (BI 6727) | Time to Deterioration in Global Health Status/Quality of Life (QOL) | NA weeks |
| Cytotoxic | Time to Deterioration in Global Health Status/Quality of Life (QOL) | 39.6 weeks |
95% CI: [0.4, 1.61]
Secondary
Time to Deterioration in Pain/ Quality of Life (QOL)
Time to deterioration in pain/ Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires. The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.
Time frame: Every 6 weeks (Up to 213 weeks )
Population: TS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Volasertib (BI 6727) | Time to Deterioration in Pain/ Quality of Life (QOL) | NA weeks |
| Cytotoxic | Time to Deterioration in Pain/ Quality of Life (QOL) | 54.1 weeks |
95% CI: [0.39, 1.93]
Secondary
Time to Deterioration in the Three Most Troublesome Disease Specific Symptoms/ Quality of Life (QOL)
Three most troublesome disease specific symptoms, defined by the patient at baseline. Patients that have defined more than 3 most troublesome symptoms have not been taken into account in the analysis. Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires. The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.
Time frame: Every 6 weeks (Up to 213 weeks)
Population: TS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Volasertib (BI 6727) | Time to Deterioration in the Three Most Troublesome Disease Specific Symptoms/ Quality of Life (QOL) | NA weeks |
| Cytotoxic | Time to Deterioration in the Three Most Troublesome Disease Specific Symptoms/ Quality of Life (QOL) | 18.9 weeks |
95% CI: [0.09, 0.77]
Secondary
Tmax; Time From Dosing to Maximum Measured Concentration of BI 6727 BS in Plasma
tmax; time from dosing to maximum measured concentration of BI 6727 BS in plasma
Time frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Volasertib (BI 6727) | Tmax; Time From Dosing to Maximum Measured Concentration of BI 6727 BS in Plasma | 2.00 hours |
Secondary
Tmax; Time From Dosing to Maximum Measured Concentration of CD 10899 BS in Plasma
tmax; time from dosing to maximum measured concentration of CD 10899 BS (metabolite of Volasertib BI 6727) in plasma
Time frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Volasertib (BI 6727) | Tmax; Time From Dosing to Maximum Measured Concentration of CD 10899 BS in Plasma | 6.07 hours |
Secondary
Vss;Apparent Volume of Distribution at Steady State Following Intravenous Administration for BI 6727 BS
Vss;apparent volume of distribution at steady state following intravenous administration for BI 6727 BS
Time frame: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration
Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Volasertib (BI 6727) | Vss;Apparent Volume of Distribution at Steady State Following Intravenous Administration for BI 6727 BS | 5690 Litres | Geometric Coefficient of Variation 25.8 |